Prognostic value of C3d-fixing, preformed donor-specific antibodies in crossmatch-positive living kidney transplantation

Transpl Immunol. 2019 Dec:57:101230. doi: 10.1016/j.trim.2019.101230. Epub 2019 Aug 6.

Abstract

The occurrence of acute antibody-mediated rejection (ABMR) is higher in flow cytometric crossmatch (FCXM)-positive patients despite desensitization. Accumulating evidence suggests a correlation between the complement-binding ability of donor-specific antibodies (DSAs) and the risk of ABMR. Here, we investigated the correlation between complement C3d-fixing ability of preformed DSA and ABMR risk, the efficacy of a desensitization protocol for patients with C3d-fixing DSA, and the risk of ABMR in 21 DSA- and FCXM-positive patients. We retrospectively analyzed the C3d-fixing ability and mean fluorescence intensity (MFI) of preformed DSA before and after desensitization. Six patients had non-C3d-fixing DSA and 15 had C3d-fixing DSA. The presence of C3d-fixing DSA before desensitization was correlated with the incidence of acute ABMR within 1 year after transplantation (p = .04) and chronic ABMR (p = .03). Moreover, the MFI of preformed DSA differed between responder and non-responder C3d-fixing DSA after desensitization (p < .0001). The C3d-fixing ability of preformed DSA with low MFI disappeared after desensitization. These results indicate that measuring DSA C3d-fixing ability may identify patients with a high risk of ABMR, especially before desensitization. CLINICAL TRIAL NOTATION: UMIN Clinical Trials Registry (UMIN-CTR) number: UMIN000033449.

Keywords: Antibody-mediated rejection; C3d; Crossmatch; Donor-specific antibody; Living kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Complement Activation
  • Complement C3d / metabolism*
  • Flow Cytometry
  • Graft Rejection / diagnosis*
  • Graft Rejection / epidemiology
  • Graft Rejection / mortality
  • Histocompatibility Testing
  • Humans
  • Incidence
  • Isoantibodies / metabolism*
  • Japan / epidemiology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Protein Binding
  • Retrospective Studies
  • Risk
  • Survival Analysis
  • Transplantation, Homologous

Substances

  • Isoantibodies
  • Complement C3d